CN101591290A - The back-end production process of synthesis of quinoline and derivative thereof - Google Patents
The back-end production process of synthesis of quinoline and derivative thereof Download PDFInfo
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- CN101591290A CN101591290A CNA2009100316342A CN200910031634A CN101591290A CN 101591290 A CN101591290 A CN 101591290A CN A2009100316342 A CNA2009100316342 A CN A2009100316342A CN 200910031634 A CN200910031634 A CN 200910031634A CN 101591290 A CN101591290 A CN 101591290A
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Abstract
The invention provides the back-end production process of a kind of synthesis of quinoline and derivative thereof.This technology is extracted the crude product quinoline with the back road of synthesis of quinoline and derivative thereof, is improved in the two-step approach alkali and technology by the neutralization of single stage method alkali.This technology adds the alkali lye neutralization with preceding road synthesis reaction solution, to reaction solution pH be 2～5; Standing and reacting liquid is treated oil phase, water layering, isolates the oil phase thing; Aqueous-phase material after will separating again carries out the alkali neutralization of second step, and controlled temperature is between 25～35 ℃, and pH is 7～8, finishes the two steps neutralization of acid-reaction liquid.The first step alkali neutralization of the present invention just makes most organic impurity separated, reduce impurity and participate in the alkali neutralization of second step, so saved in and alkali charge, weight minimizing, the content of the thick product of quinoline are improved, helping distilling purifying obtains quinoline elaboration high-quality, high yield, and has reduced the volume of equipment, artificial and power consumption, reduce cost, improved economic benefit.
Description
Technical field
The present invention relates to the production technique of synthesis of quinoline and derivative thereof, particularly the back-end production process of synthesis of quinoline and derivative thereof.
Background technology
Quinoline and derivative oxine thereof, 5 chloro-, 8 hydroxyquinolines are important intermediate of Minute Organic Synthesis, are used for synthetic medicine, agricultural chemicals and flower antistaling agent, also generally as the extraction agent of metal ion in the chemical analysis, stabilizer of hydrogen peroxide etc.The present method of synthesis of quinoline and derivative thereof is original in 1880 by Czech chemist Si Kelaopu (Skraup) and the tradition always used till today and classic methods.This method is to adopt the mixing synthesis of quinoline of aniline, glycerine, sulfuric acid and oil of mirbane chemical feedstockss such as (or oxygenants such as arsenic powder, iron trichloride); Then, synthesize corresponding quinoline heterogeneous ring compound with corresponding amino-phenol, oxygenant, sulfuric acid and glycerine again, obtained derivative products such as oxine and 5-chloro-oxine.The step of its stepwise synthesis reaction is: (1) glycerine and strong sulfuric acid response generate propenal; (2) aniline and propenal 1,2 addition become the anilino propionic aldehyde; (3) acid catalysis is cyclized into 1, the 2-dihyaroquinoline; (4) the oxydehydrogenation aromatization changes into quinoline and corresponding quinolines.And after building-up reactions finishes, from reaction solution, extract the subsequent processing method of quinoline and derivative 8 hydroxyquinolines thereof, 5 chloro-, 8 hydroxyquinolines, then still adopt in the usual Si Kelaopu single stage method alkali that uses in the industry and technology.This technology be with reactant after distillation removes, reclaims unreacted o-NP, use in the alkali extremely neutral again with acid reaction solution, filter, isolate quinoline crude product precipitation, throw out obtains the elaboration of quinoline again by methods such as recrystallization, wet distillation, distillations.Because the technology with Si Kelao popularize law synthesis of quinoline and derivative thereof fixes in people's thinking, also rare in the industry for a long time people carries out new close examination to described postchannel process.In fact, there is defective in this postchannel process.Because in the technology of the building-up reactions in preceding road, excessive sulfuric acid and glycerine reaction can generate many intermediate by-products, as: the sulfuric acid ester of β-aryl amine propenal, dihydro hydroxyquinoline, 3-hydroxy propanal, glycerine and various hydroxyl and vitriolic resin etc.These by products are in participating in N-process, and sulfuric acid will constantly be neutralized generation salt, and the corresponding sulfuric acid ester of oxy-compound is constantly hydrolysis thereupon also, discharge impurity such as the tar of acid and oxy-compound, organic phase and polymer.That is to say, in the existing single stage method alkali and technology, be with the pH7-8 that all neutralizes together of all substances in the reaction solution.So quinoline and organic impurity are got off by coprecipitation as the quinoline crude product.So not only reduced the content of quinoline in crude product; In also having increased and alkali charge; Reduce the ability of treatment facility, consumed more manpowers and power.In addition, because the tar and the polymer of reactant are to be the state that wraps up quinoline to exist, also influenced the effect of quinoline crude product recrystallization, steam distillation or distillation, corresponding quality and the yield that reduces the quinoline elaboration again.
Summary of the invention
The present invention is directed to the defective of above-mentioned existence, the back-end production process of a kind of synthesis of quinoline and derivative thereof has been proposed, purpose is by the otherwise effective technique scheme, on the basis of existing installation, improve the output and the yield of quinoline product, reduce manpower and power consumption, and improve the quality of product simultaneously.
Goal of the invention of the present invention is achieved by the following technical solution:
The present invention with synthesis of quinoline and derivative thereof after in the single stage method alkali in road and extract the technology of crude product quinoline, be improved in the two-step approach alkali and technology.Its concrete processing step is as follows:
(1) the acid synthesis reaction solution in preceding road is inserted in and in the still, after cooling, add the alkali lye neutralization, to jar in reaction solution pH be 2～5, finish the neutralization of the first step alkali;
(2) with in the first step alkali and after reaction solution left standstill 30 minutes, wait for oil phase, water layering, isolate the oil phase thing;
(3) aqueous-phase material after will separating again carries out the alkali neutralization of second step, and between 25～35 ℃ of the control neutral temperatures, pH is 7～8, then finishes the alkali neutralization of second step;
(4) filtration or separation (because of quinoline is that oily liquids must separate), washing neutralizer, acquisition quinoline crude product
Wherein, being used for neutral alkali in the described technology is that mass concentration is sodium hydroxide, the yellow soda ash of 20-35%, the mineral alkali of ammoniacal liquor.
Beneficial effect of the present invention:
(1) the two step alkali neutralisations that propose of the present invention, make in the acid synthesis reaction solution experience the first step alkali lye and after, in pH=2～5 o'clock, most organic impuritys are separated, but the purpose product is still at aqueous phase; Water is neutralized to pH=7～8 by second step again, thick product redeposition of purpose product and water sepn, impurity significantly reduces, filter or separate and washing easily, total in and alkali charge reduce;
(2) technology of the present invention is under same synthesis material, the weight of the thick product of quinoline is reduced, and content improves, help the further purification of quinoline, obtain quinoline elaboration high-quality, high yield, and the volume of equipment, energy expenditure, artificial and power charge reduce to some extent, reduce the cost of product, improved the economical efficiency of enterprise.
Description of drawings
Accompanying drawing is a main technique FB(flow block) of the present invention.
Embodiment
Embodiment one,
Prepared in laboratory quinoline 5-chloro-oxine.
(1) building-up reactions:
In the 500ml three-necked flask, add the 2-amino-4-chlorophenol 34.32g (0.24mol) and the 2-nitro-4-chlorophenol 12g (0.12mol) of exsiccant, stir adding dry glycerine 84g (0.9mol) down.After mixing, slowly drip vitriol oil 60g (0.6mol) from constant pressure funnel, drip to finish, install reflux condensing tube (top installation drying tube) rapidly, (airbath) slow fire heating on electric mantle, after treating vigorous reaction, reheat (126-130 ℃) back flow reaction 5h.Reaction mixture cooling back adds suitable quantity of water, connects the wet distillation device, reclaims 2-nitro-4-chlorophenol.
(2) back road fractional neutralization:
Embodiment one it (1):
The surplus liquid of above-mentioned steaming mass concentration 30% sodium hydroxide solution conditioned reaction liquid pH=2, pour in the separating funnel, standing demix divides the layer mutually that deoils, and aqueous phase layer neutralizes with sodium carbonate solution again, and controlled temperature is 25 ℃, pH=7 separates out precipitation, filtration washing, obtain 5-chloro-oxine crude product, content is 80%.
Embodiment one they (2):
The surplus liquid mass concentration of above-mentioned steaming is with 20% sodium carbonate solution conditioned reaction liquid pH=3, pour in the separating funnel, standing demix divides the layer mutually that deoils, and aqueous phase layer neutralizes with sodium carbonate solution again, and controlled temperature is 28 ℃, pH=7.5 separates out precipitation, filtration washing, obtain 5-chloro-oxine crude product, content is 79%.
Embodiment one they (3):
The surplus liquid of above-mentioned steaming is poured in the separating funnel with 25% ammoniacal liquor conditioned reaction liquid pH=4, and standing demix divides the layer mutually that deoils, aqueous phase layer is again with sodium carbonate solution neutralization, and controlled temperature is 29 ℃, and pH=8 separates out precipitation, filtration washing obtains 5-chloro-oxine crude product, and content is 79.5%.
Embodiment one they (4):
The surplus liquid of above-mentioned steaming is with 35% sodium hydroxide solution conditioned reaction liquid pH=5, pour in the separating funnel, standing demix divides the layer mutually that deoils, and aqueous phase layer neutralizes with sodium carbonate solution again, and controlled temperature is 30 ℃, pH=8 separates out precipitation, filtration washing, obtain 5-chloro-oxine crude product, content is 78%.
(3) crude product is purified and is elaboration:
5-chloro-oxine crude product is carried out wet distillation, treat to separate out white precipitate after the distillate cooling, suction filtration, filter cake wash with water and obtain white solid, get 5-chloro-oxine product in 50-60 ℃ of following vacuum-drying.
Calculate by product yield %=(product actual output ÷ is by the theoretical yield of amino-phenol) * 100:
Wherein: embodiment one it (1) massfraction be 99.6%, yield is 105.2% (in 2-amino-4-chlorophenol), the 5-chloro-oxine elaboration of fusing point 121-126 ℃.
Embodiment one they (2) massfraction be 99.5%, yield is 104.3%, the 5-chloro-oxine elaboration of fusing point 122-124 ℃.
Embodiment one they (3) massfraction be 99.4%, yield is 105.1%, the 5-chloro-oxine elaboration of fusing point 122-125 ℃.
Embodiment one they (4) massfraction be 99.2%, yield is 103.2%, the 5-chloro-oxine elaboration of fusing point 123-126 ℃.
Embodiment two,
Prepared in laboratory quinoline oxine.
(1) building-up reactions:
In the 1000ml three-necked flask, add the Ortho-Aminophenol 50g (0.45mol) and the o-NP 34g (0.24mol) of exsiccant, stir adding anhydrous glycerol 120g (0.1.3mol) down.After mixing, slowly drip vitriol oil 125g (0.1.25mol) from constant pressure funnel, drip and finish, install rapidly reflux condensing tube (top installation drying tube), (airbath) slow fire heating on electric mantle, when little boiling, stop heating, after question response relaxed, reheat kept little reaction 2h that boils.Reaction mixture cools off the back slightly and adds suitable quantity of water, connects the wet distillation device, reclaims 2-nitro-4-chlorophenol.
(2) back road fractional neutralization:
Embodiment one it (1):
The surplus liquid of above-mentioned steaming mass concentration 30% sodium hydroxide solution conditioned reaction liquid pH=3, pour in the separating funnel, standing demix divides the layer mutually that deoils, and aqueous phase layer neutralizes with sodium carbonate solution again, and controlled temperature is 25 ℃, pH=7 separates out precipitation, filtration washing, obtain the oxine crude product, content is 68.1%.
Embodiment one they (2):
The surplus liquid mass concentration of above-mentioned steaming is with 20% sodium carbonate solution conditioned reaction liquid pH=4, pour in the separating funnel, standing demix divides the layer mutually that deoils, and aqueous phase layer neutralizes with sodium carbonate solution again, and controlled temperature is 28 ℃, pH=7.5 separates out precipitation, filtration washing, obtain the oxine crude product, content is 67.9%.
Embodiment one they (3):
The surplus liquid of above-mentioned steaming is poured in the separating funnel with 25% ammoniacal liquor conditioned reaction liquid pH=5, and standing demix divides the layer mutually that deoils, aqueous phase layer is again with sodium carbonate solution neutralization, and controlled temperature is 29 ℃, and pH=8 separates out precipitation, filtration washing obtains the oxine crude product, and content is 67.8%.
Embodiment one they (4):
The surplus liquid of above-mentioned steaming is poured in the separating funnel with 35% sodium hydroxide solution conditioned reaction liquid pH=3, and standing demix divides the layer mutually that deoils, aqueous phase layer is again with sodium carbonate solution neutralization, and controlled temperature is 30 ℃, and pH=8 separates out precipitation, filtration washing obtains the hydroxyquinoline crude product, and content is 67.5%.
(3) crude product is purified and is elaboration:
The oxine crude product is carried out wet distillation, treat to separate out white precipitate after the distillate cooling, suction filtration, filter cake wash with water and obtain white solid, and vacuum-drying gets the oxine product under certain temperature.
Below provide subordinate list, be presented under the identical condition, the synthesis reaction solution of the synthetic oxine in laboratory adopts the experimental result of step neutralization and two step neutralisations:
Embodiment three,
One step of suitability for industrialized production quinoline neutralisation and two step neutralisations compare:
Main production equipments: among one of 2 tons of steam boiler, four of 1000L synthesis reactors, the 2000L and four of stills, five of 2000L steam distillation stills.Every batch of charging capacity: glycerine 240kg, sulfuric acid 250kg, Ortho-Aminophenol 100kg, o-NP 70kg.After building-up reactions finished, wet distillation reclaimed unreacted o-NP.
(1) in the single stage method and the acid-reaction liquid after the distillation, pH is 7～8, filter, dry, crude product oxine (wet basis) 420kg.Crude product is steam distillation, drying, pulverizing again, average every crowd of output finished product oxine 123kg, 71.2～71.6 ℃ of average content 99.18%, fusing points.
(2) adopt acid-reaction liquid after the neutralisations distillation of two steps, only need on the equipment in and valve of still bottom liquid outlet series connection, the centre is provided with glass and looks tube.All the other, charging capacity is constant, and the first step neutralizes with alkali, about still internal reaction liquid pH=3, look tube from glass and observe, oil phase and water color and luster change (the oil phase color and luster is darker) in the fluid process, the regulation and control bottom valve is isolated the about 180kg of oil phase thing, removes most of organic phase impurity; The aqueous-phase material continuation carries out in second step with alkali lye and controlled temperature is 30 ℃, and the pH value is 7～8, and filtration, washing, drying obtain crude product oxine (wet basis) 208g.Crude product on average obtains finished product 138kg again through steam distillation, drying, pulverizing, and content about 99.6%, yield are 103.8% (in Ortho-Aminophenol), 73.4～74.2 ℃ of fusing points.
Below provide subordinate list, be presented under the identical synthetic oxine processing condition, synthesis reaction solution adopts step neutralization and two to go on foot the production result of neutralisations:
To sum up, the present invention has reached the goal of the invention of expection.
Claims (3)
1, the back-end production process of synthesis of quinoline and derivative thereof, its preceding road technology building-up reactions generates acid-reaction liquid, back-end production process obtains the technology of crude product quinoline and derivative thereof for the alkali neutralisation, it is characterized in that: road, described back alkali neutralisation production technique is in the two-step approach alkali and production technique.
2, the back-end production process of synthesis of quinoline according to claim 1 and derivative thereof is characterized in that: its concrete processing step is as follows:
(1) the acid synthesis reaction solution in preceding road is inserted in and in the still, after cooling, add the alkali lye neutralization, to jar in reaction solution pH be 2～5, finish the neutralization of the first step alkali;
(2) with in the first step alkali and after reaction solution left standstill 30 minutes, wait for oil phase, water layering, isolate the oil phase thing;
(3) aqueous-phase material after will separating again carries out the alkali neutralization of second step, and between 25～35 ℃ of the control neutral temperatures, pH is 7～8, finishes the alkali neutralization of second step;
(4) filtration or separation, washing neutralizer obtain the quinoline crude product.
3, the back-end production process of synthesis of quinoline according to claim 1 and 2 and derivative thereof is characterized in that: be used for neutral alkali lye in the described technology and be mass concentration and be sodium hydroxide, the yellow soda ash of 20-35%, the mineral alkali of ammoniacal liquor.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101838237A (en) * | 2010-04-27 | 2010-09-22 | 无锡市化工研究设计院宜兴联营实验厂 | Clean production process for separating 8-hydroxyquinoline from quinoline method neutralizing solution |
| CN102267943A (en) * | 2011-07-29 | 2011-12-07 | 江苏力达宁化工有限公司 | Method for preparing 5-chloro-8-hydroxyquinoline |
| CN106986824A (en) * | 2017-05-08 | 2017-07-28 | 宜兴市宏博精细化工有限公司 | A kind of 8 oxyquinoline preparation facilities |
| CN108191753A (en) * | 2018-02-24 | 2018-06-22 | 利尔化学股份有限公司 | A kind of preparation method of 5- chloro-8-hydroxyquinolines |
| CN109279611A (en) * | 2018-11-30 | 2019-01-29 | 亚洲硅业（青海）有限公司 | The method and device of impurity in a kind of removal chlorosilane |
| CN109485603A (en) * | 2018-10-31 | 2019-03-19 | 梁敏华 | A kind of preparation method of the 8-hydroxyquinoline of no solid waste output |
-
2009
- 2009-06-19 CN CNA2009100316342A patent/CN101591290A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101838237A (en) * | 2010-04-27 | 2010-09-22 | 无锡市化工研究设计院宜兴联营实验厂 | Clean production process for separating 8-hydroxyquinoline from quinoline method neutralizing solution |
| CN101838237B (en) * | 2010-04-27 | 2011-11-09 | 无锡市化工研究设计院宜兴联营实验厂 | Clean production process for separating 8-hydroxyquinoline from quinoline method neutralizing solution |
| CN102267943A (en) * | 2011-07-29 | 2011-12-07 | 江苏力达宁化工有限公司 | Method for preparing 5-chloro-8-hydroxyquinoline |
| CN106986824A (en) * | 2017-05-08 | 2017-07-28 | 宜兴市宏博精细化工有限公司 | A kind of 8 oxyquinoline preparation facilities |
| CN108191753A (en) * | 2018-02-24 | 2018-06-22 | 利尔化学股份有限公司 | A kind of preparation method of 5- chloro-8-hydroxyquinolines |
| CN108191753B (en) * | 2018-02-24 | 2022-03-15 | 利尔化学股份有限公司 | Preparation method of 5-chloro-8-hydroxyquinoline |
| CN109485603A (en) * | 2018-10-31 | 2019-03-19 | 梁敏华 | A kind of preparation method of the 8-hydroxyquinoline of no solid waste output |
| CN109279611A (en) * | 2018-11-30 | 2019-01-29 | 亚洲硅业（青海）有限公司 | The method and device of impurity in a kind of removal chlorosilane |
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Application publication date: 20091202 |